Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

A bioinspired omniphobic surface coating on medical devices prevents thrombosis and biofouling


Thrombosis and biofouling of extracorporeal circuits and indwelling medical devices cause significant morbidity and mortality worldwide. We apply a bioinspired, omniphobic coating to tubing and catheters and show that it completely repels blood and suppresses biofilm formation. The coating is a covalently tethered, flexible molecular layer of perfluorocarbon, which holds a thin liquid film of medical-grade perfluorocarbon on the surface. This coating prevents fibrin attachment, reduces platelet adhesion and activation, suppresses biofilm formation and is stable under blood flow in vitro. Surface-coated medical-grade tubing and catheters, assembled into arteriovenous shunts and implanted in pigs, remain patent for at least 8 h without anticoagulation. This surface-coating technology could reduce the use of anticoagulants in patients and help to prevent thrombotic occlusion and biofouling of medical devices.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: TLP-coated surfaces repel whole human blood.
Figure 2: Whole blood interactions with TLP surfaces.
Figure 3: Stability and thrombogenicity of TLP surfaces.
Figure 4: Thrombogenicity of TLP-coated circuits in a porcine arteriovenous shunt model.

Similar content being viewed by others


  1. McCarthy, P.M. & Smith, W.A. Mechanical circulatory support–a long and winding road. Science 295, 998–999 (2002).

    Article  CAS  Google Scholar 

  2. Shen, J.I., Mitani, A.A., Chang, T.I. & Winkelmayer, W.C. Use and safety of heparin-free maintenance hemodialysis in the USA. Nephrol. Dial. Transplant. 28, 1589–1602 (2013).

    Article  CAS  Google Scholar 

  3. von Segesser, L.K. et al. Risk and benefit of low systemic heparinization during open heart operations. Ann. Thorac. Surg. 58, 391–398 (1994).

    Article  CAS  Google Scholar 

  4. Conn, G. et al. Is there an alternative to systemic anticoagulation, as related to interventional biomedical devices? Expert Rev. Med. Devices 3, 245–261 (2006).

    Article  CAS  Google Scholar 

  5. Werner, C., Maitz, M.F. & Sperling, C. Current strategies towards hemocompatible coatings. J. Mater. Chem. 17, 3376–3384 (2007).

    Article  CAS  Google Scholar 

  6. Cronin, R.E. & Reilly, R.F. Unfractionated heparin for hemodialysis: still the best option. Semin. Dial. 23, 510–515 (2010).

    Article  Google Scholar 

  7. Finkel, K.W. & Podoll, A.S. Complications of continuous renal replacement therapy. Semin. Dial. 22, 155–159 (2009).

    Article  Google Scholar 

  8. Shepherd, G., Mohorn, P., Yacoub, K. & May, D.W. Adverse drug reaction deaths reported in United States vital statistics, 1999–2006. Ann. Pharmacother. 46, 169–175 (2012).

    Article  Google Scholar 

  9. Peppas, N. & Langer, R. New challenges in biomaterials. Science 263, 1715–1720 (1994).

    Article  CAS  Google Scholar 

  10. Larm, O., Larsson, R. & Olsson, P. A new non-thrombogenic surface prepared by selective covalent binging of heparin via a modified reducing terminal residue. Biomater. Med. Devices Artif. Organs 11, 161–173 (1983).

    Article  CAS  Google Scholar 

  11. Bannan, S. et al. Low heparinization with heparin-bonded bypass circuits: is it a safe strategy? Ann. Thorac. Surg. 63, 663–668 (1997).

    Article  CAS  Google Scholar 

  12. Lobato, R.L. et al. Anticoagulation management during cardiopulmonary bypass: A survey of 54 North American institutions. J. Thorac. Cardiovasc. Surg. 139, 1665–1666 (2010).

    Article  Google Scholar 

  13. Thiara, A.S. et al. Comparable biocompatibility of Phisio- and Bioline-coated cardiopulmonary bypass circuits indicated by the inflammatory response. Perfusion 25, 9–16 (2010).

    Article  CAS  Google Scholar 

  14. Palanzo, D.A. et al. Effect of Carmeda® BioActive Surface coating versus Trillium™ Biopassive Surface coating of the oxygenator on circulating platelet count drop during cardiopulmonary bypass. Perfusion 16, 279–283 (2001).

    Article  CAS  Google Scholar 

  15. Suhara, H. et al. Efficacy of a new coating material, PMEA, for cardiopulmonary bypass circuits in a porcine model. Ann. Thorac. Surg. 71, 1603–1608 (2001).

    Article  CAS  Google Scholar 

  16. Smith, R.S. et al. Vascular catheters with a nonleaching poly-sulfobetaine surface modification reduce thrombus formation and microbial attachment. Sci. Transl. Med. 4, 153ra132 (2012).

    Google Scholar 

  17. Kutay, V. et al. Biocompatibility of heparin-coated cardiopulmonary bypass circuits in coronary patients with left ventricular dysfunction is superior to PMEA-coated circuits. J. Card. Surg. 21, 572–577 (2006).

    Article  Google Scholar 

  18. Reser, D. et al. Retrospective analysis of outcome data with regards to the use of Phisio®-, Bioline®- or Softline®-coated cardiopulmonary bypass circuits in cardiac surgery. Perfusion 27, 530–534 (2012).

    Article  CAS  Google Scholar 

  19. Bohn, H.F. & Federle, W. Insect aquaplaning: Nepenthes pitcher plants capture prey with the peristome, a fully wettable water-lubricated anisotropic surface. Proc. Natl. Acad. Sci. USA 101, 14138–14143 (2004).

    Article  CAS  Google Scholar 

  20. Wong, T.-S. et al. Bioinspired self-repairing slippery surfaces with pressure-stable omniphobicity. Nature 477, 443–447 (2011).

    Article  CAS  Google Scholar 

  21. Clark, L. Jr. & Gollan, F. Survival of mammals breathing organic liquids equilibrated with oxygen at atmospheric pressure. Science 152, 1755–1756 (1966).

    Article  CAS  Google Scholar 

  22. Clark, L.C. Jr. et al. Perfluorocarbons having a short dwell time in the liver. Science 181, 680–682 (1973).

    Article  CAS  Google Scholar 

  23. Moss Vision Incorporated EC Certificate 3878-2007-CE-NOR 7.0. <> Originally Issued: 2007 (2012).

  24. Castro, C.I. & Briceno, J.C. Perfluorocarbon-based oxygen carriers: review of products and trials. Artif. Organs 34, 622–634 (2010).

    PubMed  Google Scholar 

  25. Kim, P., Kreder, M.J., Alvarenga, J. & Aizenberg, J. Hierarchical or not? Effect of the length scale and hierarchy of the surface roughness on omniphobicity of lubricant-infused substrates. Nano Lett. 13, 1793–1799 (2013).

    Article  CAS  Google Scholar 

  26. Vogel, N. et al. Transparency and damage tolerance of patternable omniphobic lubricated surfaces based on inverse colloidal monolayers. Nat. Commun. 4, 2167 (2013).

    Article  Google Scholar 

  27. Stark, A.Y. et al. Surface wettability plays a significant role in gecko adhesion underwater. Proc. Natl. Acad. Sci. USA 110, 6340–6345 (2013).

    Article  CAS  Google Scholar 

  28. Nilsson, J. et al. A randomized study of coronary artery bypass surgery performed with the Resting Heart™ System utilizing a low vs a standard dosage of heparin. Interact. Cardiovasc. Thorac. Surg. 15, 834–839 (2012).

    Article  Google Scholar 

  29. Gould, S.A. et al. Fluosol-DA as a red-cell substitute in acute anemia. N. Engl. J. Med. 314, 1653–1656 (1986).

    Article  CAS  Google Scholar 

  30. Epstein, A.K. et al. Liquid-infused structured surfaces with exceptional anti-biofouling performance. Proc. Natl. Acad. Sci. USA 109, 13182–13187 (2012).

    Article  CAS  Google Scholar 

  31. Tevaearai, H.T. et al. Trillium coating of cardiopulmonary bypass circuits improves biocompatibility. Int. J. Artif. Organs 22, 629–634 (1999).

    Article  CAS  Google Scholar 

  32. Nilsson, L. et al. Heparin-coated equipment reduces complement activation during cardiopulmonary bypass in the pig. Artif. Organs 14, 46–48 (1990).

    Article  CAS  Google Scholar 

  33. Hartmann, R.C. & Conley, C.L. Studies on the initiation of blood coagulation. III. The clotting properties of canine platelet-free plasma. J. Clin. Invest. 31, 685–691 (1952).

    Article  CAS  Google Scholar 

  34. Amarnath, L.P., Srinivas, A. & Ramamurthi, A. In vitro hemocompatibility testing of UV-modified hyaluronan hydrogels. Biomaterials 27, 1416–1424 (2006).

    Article  CAS  Google Scholar 

  35. Liu, F. & Grainger, D.W. in Comprehensive Biomaterials (ed. Ducheyne, P.) (Elsevier Science, Oxford, UK, 2011).

  36. Toes, G.J. et al. Superhydrophobic modification fails to improve the performance of small diameter expanded polytetrafluoroethylene vascular grafts. Biomaterials 23, 255–262 (2002).

    Article  CAS  Google Scholar 

  37. Canaud, B. et al. Pathochemical toxicity of perfluorocarbon-5070, a liquid test performance fluid previously used in dialyzer manufacturing, confirmed in animal experiment. J. Am. Soc. Nephrol. 16, 1819–1823 (2005).

    Article  CAS  Google Scholar 

  38. Strobel, M., Lyons, C.S. & Mittal, K. Plasma Surface Modification of Polymers: Relevance to Adhesion. edn. 1. (VSP, Leiden, the Netherlands, 1994).

  39. Schröder, K. et al. Plasma-induced surface functionalization of polymeric biomaterials in ammonia plasma. Contrib. Plasma Phys. 41, 562–572 (2001).

    Article  Google Scholar 

  40. Ratner, B.D. Surface modification of polymers: chemical, biological and surface analytical challenges. Biosens. Bioelectron. 10, 797–804 (1995).

    Article  CAS  Google Scholar 

  41. Zhang, Z. et al. Polybetaine modification of PDMS microfluidic devices to resist thrombus formation in whole blood. Lab Chip 13, 1963–1968 (2013).

    Article  CAS  Google Scholar 

  42. Biological Evaluation of Medical Devices, Part 4: Selection of Tests for Interactions with Blood, 2002, Second Edition and 2006 Amendment ISO 10993-4 (Geneva, International Standards Organization, 2006).

  43. Goodman, S.L. Sheep, pig, and human platelet–material interactions with model cardiovascular biomaterials. J. Biomed. Mater. Res. 45, 240–250 (1999).

    Article  CAS  Google Scholar 

  44. Audran, M. et al. Determination of perfluorodecalin and perfluoro-N-methylcyclohexylpiperidine in rat blood by gas chromatography–mass spectrometry. J. Chromatogr. B Biomed. Sci. Appl. 745, 333–343 (2000).

    Article  CAS  Google Scholar 

  45. Kang, J.H. et al. An extracorporeal blood cleansing device for sepsis therapy. Nat. Med. 10.1038/nm.3640 (14 September 2014).

Download references


This work was supported by Defense Advanced Research Projects Agency grant N66001-11-1-4180 and contract HR0011-13-C-0025, and the Wyss Institute for Biologically Inspired Engineering at Harvard University. We thank D. Super, R. Cooper, E. Murray and J. Lee for phlebotomy, T. Ferrante for assistance with fluorescence microscopy, H. Kozakewich for assistance with histology evaluation and O. Ahanotu for assistance in preparing surfaces. Scanning electron microscopy and X-ray photoelectron spectroscopy were conducted at the Center for Nanoscale Systems at Harvard University, a member of the National Nanotechnology Infrastructure Network, which is supported by the National Science Foundation (ECS-0335765).

Author information

Authors and Affiliations



D.C.L., A.W., J.B.B., T.M.V., A.L.W., A.J., M.A., M.S., J.A. and D.E.I. designed the research. D.C.L., A.W., J.B.B., T.M.V., A.L.W., A.J., P.K., B.D.H., E.H.S., D.E.B. and S.R. performed experiments. D.C.L., A.W., J.B.B., T.M.V., A.L.W., A.J., E.H.S., M.A., M.S., J.A. and D.E.I. analyzed data. C.H., C.P.J., T.L.V., M.A. and J.A. designed, performed and analyzed the PFD leaching study. D.C.L., A.W., J.B.B., A.N., K.D., D.E.B., A.R.H., M.S. and D.E.I. designed, performed and analyzed the in vivo study. D.C.L., A.W., A.L.W., M.A., M.S., J.A. and D.E.I. wrote the paper with input from all authors.

Corresponding author

Correspondence to Donald E Ingber.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–12, Supplementary Tables 1 and 2 and Supplementary Note 1 (PDF 1086 kb)

Supplementary Movie 1

Adhesion of human blood on untreated control acrylic. Movie of human whole blood anticoagulated with 3.2% sodium citrate)adhering to an uncoated control acrylic surface. (MOV 2345 kb)

Supplementary Movie 2

Repulsion of human blood by TLP acrylic. Movie of human whole blood (anticoagulated with 3.2% sodium citrate) repelled by a TLP acrylic surface. (MOV 1572 kb)

Supplementary Movie 3

Repulsion of human blood by TLP acrylic and polypropylene. Movie of TLP acrylic (left) and control acrylic (right) being immersed in human blood, showing no adhesion on TLP. The blood is then poured out of the TLP (left) and control (right) polypropylene (PP)tubes, again showing no adhesion of blood on the TLP surface. (MOV 62666 kb)

Supplementary Movie 4

Gecko maintains adhesion to a control acrylic cylinder as it is slowly tilted from horizontal to vertical. (MOV 10737 kb)

Supplementary Movie 5

Gecko fails to adhere to a TLP-coated acrylic cylinder as it is slowly tilted from horizontal to vertical. (MOV 6433 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Leslie, D., Waterhouse, A., Berthet, J. et al. A bioinspired omniphobic surface coating on medical devices prevents thrombosis and biofouling. Nat Biotechnol 32, 1134–1140 (2014).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing